title: Down-regulation of apurinic/apyrimidinic endonuclease 1 (APE1) in spinal motor neurones under oxidative stress.
abstract: OBJECTIVE
  Apurinic/apyrimidinic endonuclease 1 (APE1) is an intermediate enzyme in base excision repair which is important for removing damaged nucleotides under normal and pathological conditions. Accumulation of damaged bases causes genome instability and jeopardizes cell survival. Our study is to examine APE1 regulation under oxidative stress in spinal motor neurones which are vulnerable to oxidative insult.
  
  
  METHODS
  We challenged the motor neurone-like cell line NSC-34 with hydrogen peroxide and delineated APE1 function by applying various inhibitors. We also examined the expression of APE1 in spinal motor neurones after spinal root avulsion in adult rats.
  
  
  RESULTS
  We showed that hydrogen peroxide induced APE1 down-regulation and cell death in a differentiated motor neurone-like cell line. Inhibiting the two functional domains of APE1, namely, DNA repair and redox domains potentiated hydrogen peroxide induced cell death. We further showed that p53 phosphorylation early after hydrogen peroxide treatment might contribute to the down-regulation of APE1. Our in vivo results similarly showed that APE1 was down-regulated after root avulsion injury in spinal motor neurones. Delay of motor neurone death suggested that APE1 might not cause immediate cell death but render motor neurones vulnerable to further oxidative insults.
  
  
  CONCLUSIONS
  We conclude that spinal motor neurones down-regulate APE1 upon oxidative stress. This property renders motor neurones susceptible to continuous challenge of oxidative stress in pathological conditions.
authors.affiliation: Department of Anatomy, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong, China; Research Center of Reproduction, Development and Growth, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Tak-Ho
authors.initials: TH
authors.lastname: Chu
authors.forename: Anchen
authors.initials: A
authors.lastname: Guo
authors.forename: Wutian
authors.initials: W
authors.lastname: Wu
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D015536:Down-Regulation; D008297:Male; D009046:Motor Neurons / Q000201:enzymology*; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000201:enzymology*
chemical_list: C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: NSC-34; base excision repair; root avulsion